Design of Trehalose-based Amide/Sulfonamide C-type Lectin Receptor Ligands.

Design of Trehalose-based Amide/Sulfonamide C-type Lectin Receptor Ligands. ChemMedChem. 2021 Jan 07;: Authors: Ryter KT, Rasheed OK, Buhl C, Evans JT Abstract Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha the (TNF) and promote the development of a Th1/Th17 immune response that may be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6΄-amide and sulfonamide α,α-D-trehalose compounds with various substituents on the aromatic ring were synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-Type Lectin Receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure-activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human Mincle specific stimulation in a HEK reporter cell line. PMID: 33415819 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research